Fungal infections are a common cause of opportunistic infections in immunocompromised persons. Among the most severe infections is fungal meningitis. Cryptococcal meningitis is the most common cause of adult meningitis in Africa, and Cryptococcus causes 15% of AIDS-related mortality globally. Amphotericin B combination antifungal is the recommended therapy for cryptococcal meningitis; however, in Sub-Saharan Africa outside of South Africa, amphotericin is rarely available in routine care. Barriers to amphotericin availability and use include cold chain shipping and storage at 4?C, IV administration, and toxicity. In the United States, the necessity on IV amphotericin administration prolongs hospitalization, increasing costs. However, an innovative orally-absorbed encochleated amphotericin B (cAMB) has been developed. In brief, this is amphotericin B wrapped in a soy-based lipoprotein (i.e. cochleate) that is absorbed and taken up by monocytes and macrophages for targeted intra-cellular delivery. As such cAMB achieves high intracellular concentrations where the phagocytosed yeast reside but low extracellular concentrations, resulting in minimal systemic and nephrotoxicity. In intramural NIH mouse studies, oral cAMB at 25 mg/kg/day with flucytosine has similar survival as injected amphotericin and flucytosine, which is considered the goal standard of therapy. Human phase I single ascending dose studies have been completed in the U.S. where 200-800mg doses have been well tolerated with only mild GI side effects observed at 800mg given as a single dose. An ongoing NIH phase II trial of chronic mucocutaneous candidiasis (n=3) in persons living with hyper-IgE Job syndrome has demonstrated safety and efficacy of 400mg cAMB taken 1-2x daily (i.e. up to 800mg/day) for >12 months. We propose to conduct phase I multiple ascending dose finding trial to determine pharmacokinetics, safety, and oral tolerability of cAMB administered in multiple doses per day in Africans. Second, we will conduct a phase II trial to investigate the 8-week safety and tolerability as consolidation therapy. Third, we will investigate microbiologic effects of cAMB on CSF Cryptococcus clearance rate in Ugandans with cryptococcal meningitis. Specific Aims: 1. Determine the pharmacokinetic, safety, and tolerability of encochleated oral cAMB given in multiple doses per day to discover the maximum safe and tolerable daily dose. 2. Determine the longer-term safety and efficacy of oral cAMB when used for cryptococcal meningitis consolidation antifungal therapy from 2 to 10 weeks after meningitis diagnosis. 3. Determine if an encochleated oral cAMB achieves non-inferior rate of CSF Cryptococcus clearance as compared to IV amphotericin B in HIV-infected Ugandans with cryptococcal meningitis. Hypotheses: We hypothesize that cAMB is well tolerated at ~25mg/kg/day in divided doses, orally absorbed and will have a non-inferior rate of CSF sterilization compared with IV amphotericin in cryptococcal meningitis.